Neuroscience. 1999;93(4):1251-62.
Buspirone modulates basal and fluoxetine-stimulated dialysate levels of dopamine, noradrenaline and serotonin in the frontal cortex of freely moving rats: activation of serotonin1A receptors and blockade of alpha2-adrenergic receptors underlie its actions.

Gobert A, Rivet JM, Cistarelli L, Melon C, Millan MJ.

Institut de Recherches Servier, Psychopharmacology Department, Croissy-sur-Seine, Paris, France.

The serotonin1A receptor partial agonist, buspirone, also displays antagonist properties at D2 receptors and is metabolized to the alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine). Herein, we examined mechanisms underlying the influence of buspirone alone, and in association with the serotonin reuptake inhibitor, fluoxetine, upon extracellular levels of serotonin, dopamine and noradrenaline simultaneously quantified in the frontal cortex of freely moving rats. Buspirone (0.01-2.5 mg/kg, s.c.) dose-dependently decreased dialysate levels of serotonin (-50%), and increased those of dopamine (+100%) and noradrenaline (+140%). The reduction by buspirone of serotonin levels was abolished by the serotonin1A receptor antagonist, WAY 100,635 (0.16), which did not, however, modify its influence upon dopamine and noradrenaline. In contrast to buspirone, the serotonin reuptake inhibitor, fluoxetine (10.0), increased frontocortical levels of serotonin (+ 120%), dopamine (+55%) and noradrenaline (+90%). Buspirone dose-dependently (0.01-2.5) decreased the induction by fluoxetine of serotonin levels yet potentiated (three-fold) its elevation of dopamine and noradrenaline levels. The serotonin1A agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (0.16), mimicked the action of buspirone in reducing resting levels of serotonin (-60%) and in enhancing those of dopamine (+135%) and noradrenaline (+165%). Like buspirone, it attenuated the influence of fluoxetine upon serotonin levels, yet facilitated its influence upon dopamine and noradrenaline levels. I




J Chromatogr Sci. 1999 Dec;37(12):462-8.
Stability-indicating high-performance liquid chromatographic assay of buspirone HCl.

Khedr A, Sakr A.

College of Pharmacy, University of Cincinnati, OH 45267-0004, USA.

The United States Pharmacopoeia high-performance liquid chromatographic (HPLC) assay method of buspirone is not able to discriminate buspirone from its degradation products. The purpose of this work is to develop a sensitive, selective, and validated stability-indicating HPLC assay for the analysis of a buspirone hydrochloride in a bulk drug. Buspirone HCI and its potential impurities and degradation products are analyzed on an Ultrasphere C18 column heated to 40 degrees C using a gradient program that contains monobasic potassium phosphate buffer solution (pH 6.9) and acetonitrile-methanol mixture (13:17) of 35% for 5 minutes, then increased to 54% in 5.5 minutes. The samples are monitored using a photo-diode array detector and integrated at 244 and 210 nm. The stress testing of buspirone HCI shows that buspirone acid hydrochloride is the major degradation product. The developed method shows a separation of buspirone degradation product and its potential impurities in one run. The stability of buspirone HCI is studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in the manufacturing process or source of the sample. The forced degradation conditions include the effect of heat, moisture, light, acid-base hydrolysis, sonication, and oxidation. The compatibility of buspirone HCI with some pharmaceutical excipients is studied under stress conditions. The linear range of buspirone HCI is between 5 and 200 ng/microL with a limit of quantitation of 2.5 ng/microL. The intraassay percentage deviation is not more than 0.38%, and the day-to-day variation was not more than 0.80%. The selectivity, repeatability, linearity, range, accuracy, sample solution stability, ruggedness, and robustness show acceptable values.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=&dopt=Abstract




Prog Neuropsychopharmacol Biol Psychiatry. 1999 Nov;23(8):1405-18.
Effects of buspirone on an animal model of tardive dyskinesia.

Queiroz CM, Frussa-Filho R.

Department of Pharmacology, Universidade Federal de Sao Paulo Escola Paulista de Medicina, Brasil.

1. The effects of buspirone were studied on an animal model of tardive dyskinesia, i.e., the quantification of orofacial dyskinesia in rats repeatedly treated with reserpine. 2. Rats were co-treated with saline [SAL] or buspirone [BUS] (3.0 mg/kg, i.p., twice daily) and vehicle [VEH] or reserpine [RES] (0.1 mg/kg, s.c., once every other day) for 19 days. On the day 20, the animals were observed for quantification of the behavioral parameters of orofacial dyskinesia: tongue protrusion and vacuous chewing movements frequencies and duration of twitching of the facial musculature. 3. Rats of the SAL + RES group exhibited a significant increase in the three behavioral parameters of orofacial dyskinesia relative to the rats of the SAL + VEH group. However, animals of the BUS + RES group showed only an increased frequency of vacuous chewing movements when compared to animals of the SAL + VEH group. In addition, the duration of the facial twitching was significantly decreased in the BUS + RES group in relation to rats of the SAL + RES group. There were no significant differences in the orofacial parameters between the BUS + VEH and the SAL + VEH groups. 4. Because it was also verified that chronic buspirone treatment was able to increase apomorphine-induced yawning behavior, the possibility is raised that buspirone attenuates reserpine-induced orofacial dyskinesia through the development of dopamine autoreceptor supersensitivity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10631766&dopt=Abstract buspirone Buspar




Eur J Pharmacol. 1994 Jun 23;259(1):75-8.
Antagonism of clonidine antinociception by buspirone and 1-(2-pyrimidinyl)-piperazine.

Cao BJ, Li WP.

Department of Pharmacology, Hunan Institute of Pharmaceutical Industry, Changsha, People's Republic of China.

The effects of pretreatment with buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) on antinociception produced by clonidine were investigated in mice. Buspirone and 1-PP dose dependently attenuated the antinociceptive action of s.c. administered clonidine in the writhing and tail-flick assays. In both assays, 1-PP was more potent than buspirone in antagonizing clonidine-induced antinociception. After s.c. pretreatment with buspirone (8 mg/kg) and 1-PP (4 mg/kg), the antinociceptive ED50 values of s.c. clonidine were significantly increased. The antagonistic effects of buspirone and 1-PP on clonidine-induced antinociception may be due to their alpha 2-adrenoceptor antagonist activity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7957598&dopt=Abstract buspirone Buspar




Gen Pharmacol. 1994 Jul;25(4):675-83.
The effects of azapirones on serotonin1A neurons of the dorsal raphe.

Matheson GK, Pfeifer DM, Weiberg MB, Michel C.

Neurobiology Laboratory, Indiana University, School of Medicine, Evansville 47714.

1. The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe were determined under the same experimental conditions. 2. Buspirone, gepirone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after administration (i.p.), their ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 data suggest that they share a similar chemical structure that binds to the 5-HT1A receptor, most likely it is "N-C-C-C-C-N" aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7958728&dopt=Abstract buspirone Buspar




Brain Res. 1995 Apr 24;677(2):213-20.
Dose-dependent effects of buspirone on behavior and cerebral glucose metabolism in rats.

Freo U, Pietrini P, Pizzolato G, Furey-Kurkjian M, Merico A, Ruggero S, Dam M, Battistin L.

Clinica delle Malattie Nervose e Mentali, Padova, Italy.

In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [14C]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7552245&dopt=Abstract buspirone Buspar




Biol Psychiatry. 1994 Apr 15;35(8):553-6.
Buspirone induced prolactin release in mania.

Yatham LN.

Department of Psychiatry, University Hospital, Vancouver, B.C.

Prolactin responses to buspirone challenge were examined in 11 manic patients and 11 healthy controls. Of the 11 manic patients, six were treated with lithium alone for 3 weeks, and the buspirone challenge test was repeated. The results showed (1) that there was no difference in prolactin response to buspirone challenge between manic patients and healthy controls, and (2) that there was no correlation between delta (delta) prolactin levels and severity of manic symptoms. Lithium treatment led to a large reduction in delta (delta) prolactin levels, which did not correlate with changes in symptom severity. These results support the possibility that 5HT1A receptors are probably not involved in the pathophysiology of mania.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8038299&dopt=Abstract buspirone Buspar




Eksp Klin Farmakol. 1994 May-Jun;57(3):7-11.
[An amplitude-interval analysis of the electrocorticogram of the normal rat and under the action of fenamine and buspirone]

[Article in Russian]

Diadenko AI, Voronina TA, Andronati SA.

The ECoG effects of natural vigilance changes were analysed on a microcomputer in rats. In addition, the effects of the psychostimulant phenamine (1 mg/kg, i.p.) and the anxiolytic buspirone (1.5 mg/kg, i.p.) were studied. The ECoG data were processed using the amplitude-interval analysis technique. The two drugs significantly modified ECoG: the maximum effect was observed within the first 30 min after buspirone administration and at 30-60 min after phenamine. Each drug affected the ECoG in its own particular manner, which was similar to their natural activation, but not identical to it. The findings provide evidence for the assumption that the activation processes play an important role in making buspirone show its psychotropic effects.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8049626&dopt=Abstract buspirone Buspar